Steroid hormones are slightly soluble in blood and are bound to plasma proteins. Approximately 60% of the estrogen is transported bound to SHBG, 20% is bound to albumin, and 20% is in the free form. Progesterone binds primarily to cortisol-binding globulin (transcortin) and albumin. Because it has relatively low binding affinity for these proteins, its circulating half-life is about 5 minutes.
Although the ovary is the primary site of estrogen production, peripheral aromatization of androgens to estrogens can generate locally high levels of estradiol-17β in some tissues. Peripheral conversion of adrenal and ovarian androgens serves as an important source of estrogen after menopause (discussed later). The fact that CYP19 (aromatase) is expressed in the breast is the basis for the use of aromatase inhibitors in the treatment of estrogen-dependent breast cancer in postmenopausal women.
•Fig. 44.29 Patternofgonadotropinsecretionthroughoutlife.Notethetransientpeaksduringgestationandearlyinfancyandthelowlevelsthereafterinchildhood.Womensubsequentlyhavemonthlycyclicbursts,withluteinizinghormone(LH)exceedingfollicle-stimulatinghormone(FSH);mendonot.Bothgendersshowincreasedgonadotropinproductionafterage50,withFSHexceedingLH.
Estrogens and progestins are degraded in the liver to inactive metabolites, conjugated with sulfate or glucuronide, and excreted in urine. Major metabolites of estradiol include estrone, estriol, and catecholestrogens (2-hydroxyestrone and 2-methoxyestrone). The major metabolite of progesterone is pregnanediol, which is conjugated with glucuronide and excreted in urine.
Ontogeny of the Reproductive Systems
Unlike most other organ systems, the reproductive systems undergo significant changes in their activity during the life span of a man or woman (
Fig. 44.29 ). Development of the reproductive systems occurs in utero and results in female or male fetuses. After birth and during infancy, the reproductive systems are largely quiescent. At puberty the hypothalamic-pituitary-gonadal axes “wake up” and the gonads begin producing sex steroids, which in turn induce the sexually dimorphic changes in appearance and behavior associated with men and women. The reproductive life span of women is set by their ovarian reserve and degree of follicular development (see earlier) and ends at menopause, usually in the fifth decade of life. Loss of estrogen production by the ovaries has a clear clinical impact on many postmenopausal women. Men continue to produce sperm throughout life but can experience a decline in androgen production (andropause), which is associated with its own clinical sequelae.
The reproductive system of women undergoes dramatic changes during pregnancy. Production of gonadotropin and gonadal steroids is switched from the maternal hypothalamic-pituitary-ovarian axis, which is strongly repressed during pregnancy, to the fetal placenta. Indeed, it is the endocrine function of fetal placental tissue that maintains a quiescent gravid uterus, (2) alters maternal physiology to ensure fetal nutrition in utero, (3) alters maternal pituitary function and mammary gland development to ensure ongoing fetal nutrition after birth, and determines the time of labor and delivery (also called parturition). The placenta also plays an important role in fetal testosterone production and male differentiation of the reproductive system before the fetal hypothalamus and pituitary develop into a functional axis.
Fertilization, Early Embryogenesis, Implantation, and Placentation
Fertilization, early embryogenesis, implantation, and early gestation are all synchronized with the human menstrual cycle (